CN103768060B - Compound tablet of ibuprofen, pseudoephedrine hydrochloride and chlorpheniramine maleate - Google Patents
Compound tablet of ibuprofen, pseudoephedrine hydrochloride and chlorpheniramine maleate Download PDFInfo
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Abstract
The invention relates to a compound tablet of ibuprofen, pseudoephedrine hydrochloride and chlorpheniramine maleate. The tablet is prepared from the following raw materials in parts by weight: 180-220 parts of ibuprofen, 28-32 parts of pseudoephedrine hydrochloride, 1.5-2.5 parts of chlorpheniramine maleate, 45-55 parts of starch, 18-22 parts of hydroxypropylcellulose, 25-35 parts of sodium carboxymethyl starch, 3-4 parts of magnesium stearate, and 1.5-3 parts of polysorbate 80. Selection and usage of each active component and auxiliary, and the preparation method of the formulation are specified and optimized more particularly, so that the prepared medicinal preparation has a more perfect comprehensive performance, and the release and stability of medicinal active components can be remarkably improved.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to compound tablet of a kind of ibuprofen, pseudoephedrine hydrochloride and chlorphenamine maleate and preparation method thereof.
Background technology
Flu is caused by virus, there is no specially good effect antiviral drugs at present, therefore mainly symptomatic treatment, with mitigation symptoms, shortens the course of disease.Flu can cause the multiple symptoms such as heating, headache, nasal obstruction, rhinorrhea, sneeze.The medicine of relief of symptoms mainly contains antipyretic analgesic, eliminates nose congested medicine, cough medicine and antihistaminic etc.The coldrex overwhelming majority on market is the compound preparation of above-mentioned several types medicine.
The product that patient reacts well in the market, cognition degree is high has ibuprofen and pseudoephedrine hydrochloride compound preparation (as Ai Feile), pseudoephedrine hydrochloride and chlorphenamine maleate compound preparation (as New contac capsule) etc., efficacy and saferry has obtained clinical extensive checking, but lack the medicine of a certain type all separately, the needs simultaneously alleviating various symptom can not be met.Market having the antipyretic analgesic contained by product (as paracetamol) that many components can alleviate various symptom of catching a cold is acetaminophen, and be worse than ibuprofen to the effect of bringing down a fever of more than 39.2 DEG C, and untoward reaction is more, safety is far worse than ibuprofen, non-best choice.
Prior art discloses the technical scheme of compound preparation ibuprofen (antipyretic-antalgic), pseudoephedrine hydrochloride (elimination nasal congestion) and chlorphenamine maleate (antihistamine) compatibility formed, three kinds of compositions of this compound preparation are widely used clinically, determined curative effect, steady quality, safe and reliable, triplicity can alleviate cold symptoms from different perspectives, patient is taken more convenient, evident in efficacy, safety is good.
As, China application CN102349900A discloses a kind of preparation technology treating the compound capsule of flu, comprise: the preparation of A. slow-releasing granules: by 60% ~ 90% of effective dose ibuprofen, the pseudoephedrine hydrochloride of effective dose and 99.5% ~ 99.95% of appropriate hydroxypropyl emthylcellulose pulverized 80 ~ 200 mesh sieves respectively, with efficient wet granulator mix homogeneously, the hydroxypropyl emthylcellulose of surplus being dissolved in percentage by volume is be mixed with the Gonak that mass percent is 0.5% ~ 2% in the alcoholic solution of 40% ~ 60% again, add this Gonak to granulate at a high speed, dry, obtain slow-releasing granules, B. the preparation of solid dispersion immediate-release granules: the chlorphenamine maleate of effective dose is mixed homogeneously with polyethylene glycol 6000, pulverize with micro-powder crusher, powder particle diameter reaches more than 200 orders, then Tween 80 aqueous solution is added, mix homogeneously, prepares solid dispersion by grinding powerful in mixture Place grinding machine, the solid dispersion of gained is added ibuprofen and cross-linked pvp, the lactose of surplus, granulate with the alcoholic solution that percentage by volume is 60 ~ 80%, 40 DEG C are dried to without moisture, make immediate-release granules, C. by above-mentioned slow-releasing granules and immediate-release granules mixing, lubricant is added, mix homogeneously, routinely obtained capsule.
In addition, China application CN101700245A discloses a kind of compound medicine for the treatment of flu, it includes the ibuprofen of effective amount, pseudoephedrine hydrochloride and chlorphenamine maleate active component, and appropriate pharmaceutic adjuvant, it is characterized in that: the ibuprofen of part effective dose and the pseudoephedrine hydrochloride of effective dose are made slow releasing preparation, described slow releasing preparation is gastric floating slow-release granular preparation, it is by 60% ~ 90% of effective dose ibuprofen, pseudoephedrine hydrochloride and hydroxypropyl emthylcellulose pulverize and sieve respectively, put in fluid bed granulator fluid bed, mix homogeneously, be heated to 60 ~ 80 DEG C, hydroxypropyl emthylcellulose is dissolved in alcoholic solution and is configured to Gonak, with Gonak spray granulation, be drying to obtain, the chlorphenamine maleate of surplus ibuprofen and effective dose is made quick releasing formulation, and described quick releasing formulation is solid dispersion immediate-release granules preparation, it is mixed homogeneously with polyethylene glycol 6000 by chlorphenamine maleate, pulverizes with micro-powder crusher, adds Tween 80 solution, mix homogeneously, mixture put grinding in ball grinder and prepares solid dispersion, solid dispersion is added the ibuprofen of cross-linked pvp, lactose and surplus, granulate with alcoholic solution, dry obtained, again slow releasing preparation and quick releasing formulation are made various pharmaceutical preparation according to a conventional method.
China application CN1473568 discloses a kind of pharmaceutical composition for the treatment of flu, contains: a) ibuprofen in its preparation; B) pseudoephedrine hydrochloride; C) chlorphenamine maleate.Concrete prescription is as follows: ibuprofen 200mg, pseudoephedrine hydrochloride 30mg, chlorphenamine maleate 2mg, amylum pregelatinisatum 100mg, carboxymethylstach sodium 20mg, lactose 35mg, 5% starch slurry are appropriate, magnesium stearate 2mg, Pulvis Talci 11mg.During preparation, ibuprofen, pseudoephedrine hydrochloride, chlorphenamine maleate were pulverized 100 mesh sieves, for subsequent use.By ibuprofen, pseudoephedrine hydrochloride, chlorphenamine maleate, amylum pregelatinisatum, carboxymethylstach sodium, lactose equal increments mix homogeneously, add appropriate 5% starch slurry soft material and cross 16 mesh sieves granulations, dry 3 hours in 50 DEG C, cross 18 mesh sieve granulate, add magnesium stearate, Pulvis Talci mix homogeneously, beat sheet.
But above-mentioned preparation each component blood concentration curve difference after taking is large, effectively can not play synergism, be unfavorable for applying, in view of this, special proposition the present invention.
Summary of the invention
The first object of the present invention is to provide the compound tablet of a kind of high-quality ibuprofen, pseudoephedrine hydrochloride and chlorphenamine maleate, this compound tablet has desirable stability, dissolution, and there is desirable drug release effect, clinical, there is more significant drug effect.
For achieving the above object.The present invention adopts following technical scheme:
A compound tablet for ibuprofen, pseudoephedrine hydrochloride and chlorphenamine maleate, is prepared from by the raw material comprising following weight portion: ibuprofen 180-220 part, pseudoephedrine hydrochloride 28-32 part, chlorphenamine maleate 1.5-2.5 part, starch 45-55 part, hyprolose 18-22 part, microcrystalline Cellulose 25-35 part, carboxymethyl starch sodium 12-16 part, magnesium stearate 3-4 part, polyoxyethylene sorbitan monoleate 1.5-3 part.
Further, be preferably prepared from by the raw material comprising following weight portion: ibuprofen 200 parts, pseudoephedrine hydrochloride 30 parts, chlorphenamine maleate 2 parts, starch 50 parts, hyprolose 20 parts, microcrystalline Cellulose 30 parts, carboxymethyl starch sodium 14 parts, magnesium stearate 3.6 parts, polyoxyethylene sorbitan monoleate 1.8 parts.
More preferably, every sheet is containing ibuprofen 200mg, pseudoephedrine hydrochloride 30mg, chlorphenamine maleate 2mg.
In prescription of the present invention, select starch, hyprolose, microcrystalline Cellulose, carboxymethyl starch sodium, magnesium stearate and Polysorbate as adjuvant, compare with the compound preparation of chlorphenamine maleate with existing ibuprofen, pseudoephedrine hydrochloride, prescription is more simple, and being combined with of above-mentioned adjuvant helps gained compound tablet and realize better stability and desirable drug release.
Meanwhile, the application has also made adjustment to traditional preparation method, by making improvement to the preparation method of compound tablet, guarantees the quality of the pharmaceutical preparations further.
Particularly, the preparation method of compound tablet of the present invention, is characterized in that, comprises the steps:
(1) get the starch of recipe quantity, add appropriate purified water and be uniformly mixed obtained starch suspension; The polyoxyethylene sorbitan monoleate getting recipe quantity joins in the purified water being equivalent to self 20 times amount, boils, and slowly joins in starch suspension, stirs, heating, and the addition of adjustment purified water, makes obtained 5-10% starch slurry, let cool to 50-60 DEG C, for subsequent use;
(2) by the microcrystalline Cellulose equal increments mix homogeneously of the hyprolose of the pseudoephedrine hydrochloride of recipe quantity 10-20% ibuprofen, recipe quantity, recipe quantity 20-40%, recipe quantity 40-50%, add appropriate amount of starch slurry soft material processed and cross 18 mesh sieves granulations, obtain granule a;
(3) by the carboxymethyl starch sodium equal increments mix homogeneously of the ibuprofen of recipe quantity 50-60%, surplus hyprolose and recipe quantity 60-70%, add appropriate amount of starch slurry soft material processed and cross 18 mesh sieves granulations, obtain granule b;
(4) by the chlorphenamine maleate of the ibuprofen of surplus, recipe quantity, the microcrystalline Cellulose of surplus and carboxymethyl starch sodium equal increments mix homogeneously, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule c;
(5) granule a, b, c are mixed, dry 2-4 hour in 40-50 DEG C, cross 16 mesh sieve granulate, add magnesium stearate, mix homogeneously, tabletting.
In above-mentioned preparation method, by active component reasonable distribution, granulate several times, then mixed pressuring plate in addition.And all active component mix with adjuvant by the preparation method employing of routine, the wet grain of system again, rear tabletting, or ibuprofen is granulated separately, by pseudoephedrine hydrochloride and chlorphenamine maleate mixing granulation, rear mixed pressuring plate etc., but the dissolution rate that existing above-mentioned preparation is in use found ibuprofen, pseudoephedrine hydrochloride and chlorphenamine maleate is unsatisfactory, causes cannot forming obvious cooperative effect each other.
Equal increments of the present invention is mixed into existing method, is specially those skilled in the art and grasps.
And present inventor is in the favorite outer discovery of research process, when by ibuprofen reasonable distribution, granulate respectively with pseudoephedrine hydrochloride and chlorphenamine maleate respectively, and the ibuprofen of surplus is additionally granulated separately, coordinate the comprehensive therapeutic effect that significantly can improve compound preparation by carrying out reasonably screening to adjuvant, and significantly improve stability and the dissolution of tablet.
The present invention has made optimization to each step in preparation method further:
Described in step (1), appropriate purified water is specifically as the criterion with obtained starch suspension, and if purified water weight is 1-5 times of starch weight etc., the present invention is not particularly limited.
Slowly adding the preferably control joining day described in step (1) is 3-5min.
Described step 2 is specially: by the microcrystalline Cellulose equal increments mix homogeneously of the hyprolose of the pseudoephedrine hydrochloride of recipe quantity 15% ibuprofen, recipe quantity, recipe quantity 30%, recipe quantity 45%, add appropriate amount of starch slurry soft material processed and cross 18 mesh sieves granulations, obtain granule a.
Described step 3 is specially: by the carboxymethyl starch sodium equal increments mix homogeneously of the ibuprofen of recipe quantity 55%, surplus hyprolose and recipe quantity 65%, adds appropriate amount of starch slurry soft material processed and crosses 18 mesh sieves granulations, obtain granule b.
The starch slurry weight ratio that wherein can also add in preferred steps 2,3,4 is 2-4:4-5:2-3.
Described step 5 is specially: granule a, b, c are mixed, and dries 3 hours in 45 DEG C, crosses 16 mesh sieve granulate, adds magnesium stearate, mix homogeneously, tabletting.
The present invention limits more specifically by having made the selection of each active component and adjuvant and the preparation method of consumption and preparation and optimizes, make prepared pharmaceutical preparation have more preferably combination property, significantly improve release and the stability of active constituents of medicine.
Accompanying drawing explanation
Fig. 1 is the drug-time curve of ibuprofen, and wherein abscissa is the time (h), and vertical coordinate is blood drug level (mg/L);
Fig. 2 is the drug-time curve of pseudoephedrine, and wherein abscissa is the time (h), and vertical coordinate is blood drug level (μ g/L);
Fig. 3 is the drug-time curve of chlorphenamine, and wherein abscissa is the time (h), and vertical coordinate is blood drug level (μ g/L).
Detailed description of the invention
To give an actual example description to the principle of the invention and feature below, example, only for explaining the present invention, is not intended to limit scope of the present invention.
Embodiment 1
Ibuprofen 200g, pseudoephedrine hydrochloride 30g, chlorphenamine maleate 2g, starch 50g, hyprolose 20g, microcrystalline Cellulose 30g, carboxymethyl starch sodium 14g, magnesium stearate 3.6g, polyoxyethylene sorbitan monoleate 1.8g.
Preparation process is:
(1) get the starch of recipe quantity, add 100g purified water and be uniformly mixed obtained starch suspension; The polyoxyethylene sorbitan monoleate getting recipe quantity joins in the purified water being equivalent to self 20 times amount, boils, and slowly joins in starch suspension, joining day 4min, stirs, heating, and the addition of adjustment purified water, makes obtained 8% starch slurry, let cool to 50-60 DEG C, for subsequent use;
(2) by the microcrystalline Cellulose equal increments mix homogeneously of the hyprolose of the pseudoephedrine hydrochloride of recipe quantity 15% ibuprofen, recipe quantity, recipe quantity 30%, recipe quantity 45%, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule a;
(3) by the carboxymethyl starch sodium equal increments mix homogeneously of the ibuprofen of recipe quantity 55%, surplus hyprolose and recipe quantity 65%, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule b;
(4) by the chlorphenamine maleate of the ibuprofen of surplus, recipe quantity, the microcrystalline Cellulose of surplus and carboxymethyl starch sodium equal increments mix homogeneously, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule c; The starch slurry weight ratio wherein added in step 2,3,4 is 3:4.5:2.5;
(5) granule a, b, c are mixed, dry 3 hours in 45 DEG C, cross 16 mesh sieve granulate, add magnesium stearate, mix homogeneously, tabletting, be pressed into 1000.
Embodiment 2
Ibuprofen 180g, pseudoephedrine hydrochloride 32g, chlorphenamine maleate 2.5g, starch 50g, hyprolose 20g, microcrystalline Cellulose 26g, carboxymethyl starch sodium 13g, magnesium stearate 3g, polyoxyethylene sorbitan monoleate 1.5g.
Preparation process is:
(1) get the starch of recipe quantity, add 100g purified water and be uniformly mixed obtained starch suspension; The polyoxyethylene sorbitan monoleate getting recipe quantity joins in the purified water being equivalent to self 20 times amount, boils, and slowly joins in starch suspension, joining day 4min, stirs, heating, and the addition of adjustment purified water, makes obtained 10% starch slurry, let cool to 50-60 DEG C, for subsequent use;
(2) by the microcrystalline Cellulose equal increments mix homogeneously of the hyprolose of the pseudoephedrine hydrochloride of recipe quantity 15% ibuprofen, recipe quantity, recipe quantity 30%, recipe quantity 45%, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule a;
(3) by the carboxymethyl starch sodium equal increments mix homogeneously of the ibuprofen of recipe quantity 55%, surplus hyprolose and recipe quantity 65%, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule b;
(4) by the chlorphenamine maleate of the ibuprofen of surplus, recipe quantity, the microcrystalline Cellulose of surplus and carboxymethyl starch sodium equal increments mix homogeneously, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule c; The starch slurry weight ratio wherein added in step 2,3,4 is 3:4.5:2.5;
(5) granule a, b, c are mixed, dry 3 hours in 45 DEG C, cross 16 mesh sieve granulate, add magnesium stearate, mix homogeneously, tabletting, be pressed into 1000.
Embodiment 3
Ibuprofen 220g, pseudoephedrine hydrochloride 32g, chlorphenamine maleate 2.0g, starch 47g, hyprolose 18g, microcrystalline Cellulose 30g, carboxymethyl starch sodium 16g, magnesium stearate 4g, polyoxyethylene sorbitan monoleate 1.8g.
Preparation process is:
(1) get the starch of recipe quantity, add 140g purified water and be uniformly mixed obtained starch suspension; The polyoxyethylene sorbitan monoleate getting recipe quantity joins in the purified water being equivalent to self 20 times amount, boils, and slowly joins in starch suspension, joining day 3min, stirs, heating, and the addition of adjustment purified water, makes obtained 8% starch slurry, let cool to 50-60 DEG C, for subsequent use;
(2) by the microcrystalline Cellulose equal increments mix homogeneously of the hyprolose of the pseudoephedrine hydrochloride of recipe quantity 10% ibuprofen, recipe quantity, recipe quantity 20%, recipe quantity 40%, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule a;
(3) by the carboxymethyl starch sodium equal increments mix homogeneously of the ibuprofen of recipe quantity 50%, surplus hyprolose and recipe quantity 60%, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule b;
(4) by the chlorphenamine maleate of the ibuprofen of surplus, recipe quantity, the microcrystalline Cellulose of surplus and carboxymethyl starch sodium equal increments mix homogeneously, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule c; The starch slurry weight ratio wherein added in step 2,3,4 is 2:4:3;
(5) granule a, b, c are mixed, dry 4 hours in 50 DEG C, cross 16 mesh sieve granulate, add magnesium stearate, mix homogeneously, tabletting, be pressed into 1000.
Embodiment 4
Ibuprofen 200g, pseudoephedrine hydrochloride 28g, chlorphenamine maleate 1.5g, starch 55g, hyprolose 22g, microcrystalline Cellulose 28g, carboxymethyl starch sodium 15g, magnesium stearate 3g, polyoxyethylene sorbitan monoleate 2.5g.
Preparation process is:
(1) get the starch of recipe quantity, add 100g purified water and be uniformly mixed obtained starch suspension; The polyoxyethylene sorbitan monoleate getting recipe quantity joins in the purified water being equivalent to self 20 times amount, boils, and slowly joins in starch suspension, joining day 4min, stirs, heating, and the addition of adjustment purified water, makes obtained 8% starch slurry, let cool to 50-60 DEG C, for subsequent use;
(2) by the microcrystalline Cellulose equal increments mix homogeneously of the hyprolose of the pseudoephedrine hydrochloride of recipe quantity 15% ibuprofen, recipe quantity, recipe quantity 30%, recipe quantity 45%, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule a;
(3) by the carboxymethyl starch sodium equal increments mix homogeneously of the ibuprofen of recipe quantity 55%, surplus hyprolose and recipe quantity 65%, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule b;
(4) by the chlorphenamine maleate of the ibuprofen of surplus, recipe quantity, the microcrystalline Cellulose of surplus and carboxymethyl starch sodium equal increments mix homogeneously, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule c; The starch slurry weight ratio wherein added in step 2,3,4 is 3:4.5:2.5;
(5) granule a, b, c are mixed, dry 3 hours in 45 DEG C, cross 16 mesh sieve granulate, add magnesium stearate, mix homogeneously, tabletting, be pressed into 1000.
Embodiment 5
Ibuprofen 210g, pseudoephedrine hydrochloride 30g, chlorphenamine maleate 1.8g, starch 53g, hyprolose 19g, microcrystalline Cellulose 33g, carboxymethyl starch sodium 13g, magnesium stearate 4g, polyoxyethylene sorbitan monoleate 2.8g.
Preparation process is:
(1) get the starch of recipe quantity, add 130g purified water and be uniformly mixed obtained starch suspension; The polyoxyethylene sorbitan monoleate getting recipe quantity joins in the purified water being equivalent to self 20 times amount, boils, and slowly joins in starch suspension, joining day 5min, stirs, heating, and the addition of adjustment purified water, makes obtained 5% starch slurry, let cool to 50-60 DEG C, for subsequent use;
(2) by the microcrystalline Cellulose equal increments mix homogeneously of the hyprolose of the pseudoephedrine hydrochloride of recipe quantity 20% ibuprofen, recipe quantity, recipe quantity 40%, recipe quantity 45%, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule a;
(3) by the carboxymethyl starch sodium equal increments mix homogeneously of the ibuprofen of recipe quantity 60%, surplus hyprolose and recipe quantity 70%, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule b;
(4) by the chlorphenamine maleate of the ibuprofen of surplus, recipe quantity, the microcrystalline Cellulose of surplus and carboxymethyl starch sodium equal increments mix homogeneously, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule c; The starch slurry weight ratio wherein added in step 2,3,4 is 4:5:2;
(5) granule a, b, c are mixed, dry 2 hours in 40 DEG C, cross 16 mesh sieve granulate, add magnesium stearate, mix homogeneously, tabletting, be pressed into 1000.
Embodiment 6
Ibuprofen 180g, pseudoephedrine hydrochloride 31g, chlorphenamine maleate 2.4g, starch 50g, hyprolose 22g, microcrystalline Cellulose 25g, carboxymethyl starch sodium 12g, magnesium stearate 4g, polyoxyethylene sorbitan monoleate 3g.
Preparation process is:
(1) get the starch of recipe quantity, add 100g purified water and be uniformly mixed obtained starch suspension; The polyoxyethylene sorbitan monoleate getting recipe quantity joins in the purified water being equivalent to self 20 times amount, boils, and slowly joins in starch suspension, joining day 4min, stir, heating, the addition of adjustment purified water, make obtained 5-10% starch slurry, let cool to 50-60 DEG C, for subsequent use;
(2) by the microcrystalline Cellulose equal increments mix homogeneously of the hyprolose of the pseudoephedrine hydrochloride of recipe quantity 15% ibuprofen, recipe quantity, recipe quantity 30%, recipe quantity 45%, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule a;
(3) by the carboxymethyl starch sodium equal increments mix homogeneously of the ibuprofen of recipe quantity 55%, surplus hyprolose and recipe quantity 65%, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule b;
(4) by the chlorphenamine maleate of the ibuprofen of surplus, recipe quantity, the microcrystalline Cellulose of surplus and carboxymethyl starch sodium equal increments mix homogeneously, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule c; The starch slurry weight ratio wherein added in step 2,3,4 is 3:4.5:2.5;
(5) granule a, b, c are mixed, dry 3 hours in 45 DEG C, cross 16 mesh sieve granulate, add magnesium stearate, mix homogeneously, tabletting, be pressed into 1000.
Embodiment 7
Ibuprofen 200g, pseudoephedrine hydrochloride 30g, chlorphenamine maleate 2g, starch 50g, hyprolose 20g, microcrystalline Cellulose 30g, carboxymethyl starch sodium 14g, magnesium stearate 3.6g, polyoxyethylene sorbitan monoleate 1.8g.
Preparation process is:
(1) get the starch of recipe quantity, add 100g purified water and be uniformly mixed obtained starch suspension; The polyoxyethylene sorbitan monoleate getting recipe quantity joins in the purified water being equivalent to self 20 times amount, boils, and slowly joins in starch suspension, joining day 3min, stirs, heating, and the addition of adjustment purified water, makes obtained 10% starch slurry, let cool to 50-60 DEG C, for subsequent use;
(2) by the microcrystalline Cellulose equal increments mix homogeneously of the hyprolose of the pseudoephedrine hydrochloride of recipe quantity 20% ibuprofen, recipe quantity, recipe quantity 30%, recipe quantity 40%, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule a;
(3) by the carboxymethyl starch sodium equal increments mix homogeneously of the ibuprofen of recipe quantity 60%, surplus hyprolose and recipe quantity 60%, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule b;
(4) by the chlorphenamine maleate of the ibuprofen of surplus, recipe quantity, the microcrystalline Cellulose of surplus and carboxymethyl starch sodium equal increments mix homogeneously, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule c; The starch slurry weight ratio wherein added in step 2,3,4 is 3:4:3;
(5) granule a, b, c are mixed, dry 3 hours in 45 DEG C, cross 16 mesh sieve granulate, add magnesium stearate, mix homogeneously, tabletting, be pressed into 1000.
Test example 1 pharmacodynamics test
Test drug:
The present invention: embodiment 1 product;
Reference substance: Buluoweima that quick, every sheet is containing ibuprofen 200mg, pseudoephedrine hydrochloride 30mg, chlorphenamine maleate 2mg; Authentication code: the accurate word H20090264 of traditional Chinese medicines.
Experimenter selects:
By 200 experimenters, men and women half and half, age 25-35 year, be divided into 2 groups at random, often organize 100 example.
Administering mode:
The two groups of experimenters oral embodiment of the present invention 1 product and reference substance respectively, every day 1 time, each one, takes medicine and uses 200ml warm water delivery service, can drink water after the 2h that takes medicine, feed unified standard meal after 4h.
Sampling:
Experimenter before administration after (0h) and administration 0.25,0.5,1.0,1.5,2.0,3.0,4.0,6.0,8.0,12.0,24.0,36.0,48.0h gathers cubital venous blood 5ml, put EDTA anticoagulant tube, the centrifugal 10min of 4000r/min, separated plasma,-20 DEG C of preservations, to be measured.
Condition determination:
Ibuprofen:
Chromatographic column is Synergi4u Polar-RP(4.6mm × 250mm, 4 μm); Column temperature is 40 DEG C; Determined wavelength 220nm; Mobile phase is acetonitrile-20mmolL
-1phosphate buffer (pH4.0) (27:73); Flow is 1.0mLmin
-1.
Chlorphenamine and pseudoephedrine:
Chromatographic condition chromatographic column is Thermo Hypurity C18(2.1mm × 150mm, 5 μm); Mobile phase is methanol-20mmolL
-1methylamine (containing 0.1% formic acid) (70:30); Flow is 0.25mLmin
-1; Column temperature is 40 DEG C, auto injection bottle temperature 15 DEG C.
Mass Spectrometry Conditions
Monitor by ESI+MRM mode; Chlorphenamine: monitoring ion is m/z275.2m/z230.2, taper hole voltage is 15eV, and collision energy is 20V; Pseudoephedrine: monitoring ion is m/z166.5m/z148.5, taper hole voltage is 15eV, and collision energy is 15V; Interior mark imipramine: monitoring ion is m/z281.3m/z85.7, taper hole voltage is 15eV, and collision energy is 20V.Capillary voltage: 3.5kV; Source temperature: 100 DEG C; Desolventizing gas temperature: 350 DEG C; Taper hole gas flow: 50Lh
-1; Desolventizing gas flow: 350Lh
-1; Multiplier:700V; LM1 and LM2 resolution is 11, ion energy voltage (1): 0.5V; Ion energy voltage (2): 3V; Collision air pressure: 2.8 × 10
-2kPa.
Result:
See Fig. 1-3 ,-◆-be reference substance plasma concentration curve ,-■-be embodiment 1 product plasma concentration curve.Therefrom can find out, product of the present invention has more consistent blood drug level variation tendency, and product plasma concentration curve of the present invention change is more mild, is beneficial to the performance of drug effect.
Test example 2 stability test
Content of the test and result
Accelerated test: sample thief, is placed in temperature 40 DEG C ± 2 DEG C, places 6 months under relative humidity 75% ± 5% condition, respectively at the 1st, 2,3, sampling in June, investigate indices, the results are shown in Table 1.
Long term test: sample thief, is placed in 25 DEG C ± 2 DEG C, places under relative humidity 60% ± 10% condition, respectively at sampling in the 3rd, 6,9,12,18,24 month, investigates indices, the results are shown in Table 2.
Subjects:
Experimental group: embodiment 1 product (every sheet is containing ibuprofen 200mg, pseudoephedrine hydrochloride 30mg, chlorphenamine maleate 2mg);
Matched group: Buluoweima that quick, every sheet is containing ibuprofen 200mg, pseudoephedrine hydrochloride 30mg, chlorphenamine maleate 2mg; Authentication code: the accurate word H20090264 of traditional Chinese medicines.
Table 1 accelerated test result
Table 2 long-term test results
Although describe the present invention in detail with most preferred embodiment above, those skilled in the art should know, under the prerequisite not departing from inventive concept and spirit, any improvement make the present invention and modification, still belong within the scope of protection of present invention.
Claims (7)
1. a compound tablet for ibuprofen, pseudoephedrine hydrochloride and chlorphenamine maleate, is characterized in that: be prepared from by the raw material comprising following weight portion: ibuprofen 180-220 part, pseudoephedrine hydrochloride 28-32 part, chlorphenamine maleate 1.5-2.5 part, starch 45-55 part, hyprolose 18-22 part, microcrystalline Cellulose 25-35 part, carboxymethyl starch sodium 12-16 part, magnesium stearate 3-4 part, polyoxyethylene sorbitan monoleate 1.5-3 part;
The preparation method of described compound tablet, comprises the steps:
(1) get the starch of recipe quantity, add appropriate purified water and be uniformly mixed obtained starch suspension; The polyoxyethylene sorbitan monoleate getting recipe quantity joins in the purified water being equivalent to self 20 times amount, boils, and slowly joins in starch suspension, stirs, heating, and the addition of adjustment purified water, makes obtained 5-10% starch slurry, let cool to 50-60 DEG C, for subsequent use;
(2) by the microcrystalline Cellulose equal increments mix homogeneously of the hyprolose of the pseudoephedrine hydrochloride of recipe quantity 10-20% ibuprofen, recipe quantity, recipe quantity 20-40%, recipe quantity 40-50%, add appropriate amount of starch slurry soft material processed and cross 18 mesh sieves granulations, obtain granule a;
(3) by the carboxymethyl starch sodium equal increments mix homogeneously of the ibuprofen of recipe quantity 50-60%, surplus hyprolose and recipe quantity 60-70%, add appropriate amount of starch slurry soft material processed and cross 18 mesh sieves granulations, obtain granule b;
(4) by the chlorphenamine maleate of the ibuprofen of surplus, recipe quantity, the microcrystalline Cellulose of surplus and carboxymethyl starch sodium equal increments mix homogeneously, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule c;
(5) granule a, b, c are mixed, dry 2-4 hour in 40-50 DEG C, cross 16 mesh sieve granulate, add magnesium stearate, mix homogeneously, tabletting.
2. compound tablet according to claim 1, it is characterized in that, be prepared from by the raw material comprising following weight portion: ibuprofen 200 parts, pseudoephedrine hydrochloride 30 parts, chlorphenamine maleate 2 parts, starch 50 parts, hyprolose 20 parts, microcrystalline Cellulose 30 parts, carboxymethyl starch sodium 14 parts, magnesium stearate 3.6 parts, polyoxyethylene sorbitan monoleate 1.8 parts.
3. compound tablet according to claim 1 and 2, is characterized in that, every sheet is containing ibuprofen 200mg, pseudoephedrine hydrochloride 30mg, chlorphenamine maleate 2mg.
4. the preparation method of compound tablet described in any one of claim 1-3, is characterized in that, comprise the steps:
(1) get the starch of recipe quantity, add appropriate purified water and be uniformly mixed obtained starch suspension; The polyoxyethylene sorbitan monoleate getting recipe quantity joins in the purified water being equivalent to self 20 times amount, boils, and slowly joins in starch suspension, stirs, heating, and the addition of adjustment purified water, makes obtained 5-10% starch slurry, let cool to 50-60 DEG C, for subsequent use;
(2) by the microcrystalline Cellulose equal increments mix homogeneously of the hyprolose of the pseudoephedrine hydrochloride of recipe quantity 10-20% ibuprofen, recipe quantity, recipe quantity 20-40%, recipe quantity 40-50%, add appropriate amount of starch slurry soft material processed and cross 18 mesh sieves granulations, obtain granule a;
(3) by the carboxymethyl starch sodium equal increments mix homogeneously of the ibuprofen of recipe quantity 50-60%, surplus hyprolose and recipe quantity 60-70%, add appropriate amount of starch slurry soft material processed and cross 18 mesh sieves granulations, obtain granule b;
(4) by the chlorphenamine maleate of the ibuprofen of surplus, recipe quantity, the microcrystalline Cellulose of surplus and carboxymethyl starch sodium equal increments mix homogeneously, add starch slurry soft material and cross 18 mesh sieves granulations, obtain granule c;
(5) granule a, b, c are mixed, dry 2-4 hour in 40-50 DEG C, cross 16 mesh sieve granulate, add magnesium stearate, mix homogeneously, tabletting.
5. preparation method according to claim 4, it is characterized in that, described step 2 is specially: by the microcrystalline Cellulose equal increments mix homogeneously of the hyprolose of the pseudoephedrine hydrochloride of recipe quantity 15% ibuprofen, recipe quantity, recipe quantity 30%, recipe quantity 45%, add appropriate amount of starch slurry soft material processed and cross 18 mesh sieves granulations, obtain granule a.
6. preparation method according to claim 4, it is characterized in that, described step 3 is specially: by the carboxymethyl starch sodium equal increments mix homogeneously of the ibuprofen of recipe quantity 55%, surplus hyprolose and recipe quantity 65%, add appropriate amount of starch slurry soft material processed and cross 18 mesh sieves granulations, obtain granule b.
7. preparation method according to claim 4, is characterized in that, described step 5 is specially: granule a, b, c are mixed, and dries 3 hours in 45 DEG C, crosses 16 mesh sieve granulate, adds magnesium stearate, mix homogeneously, tabletting.
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| CN201410038993.1A CN103768060B (en) | 2014-01-26 | 2014-01-26 | Compound tablet of ibuprofen, pseudoephedrine hydrochloride and chlorpheniramine maleate |
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| CN201410038993.1A CN103768060B (en) | 2014-01-26 | 2014-01-26 | Compound tablet of ibuprofen, pseudoephedrine hydrochloride and chlorpheniramine maleate |
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